Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor-Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity.

Cancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor-targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)-targeting group (benzenesulfonamide) are synthesized. Phototherapy of tumor cells markedly amplifies ER stress and promotes tumor antigen release, as the ER is required for protein synthesis, secretion, and transport. More importantly, different electron-donating or -withdrawing substitutions are introduced into benzenesulfonamide to modulate the nonradiative decay pathways through intramolecular charge transfer, including singlet-triplet intersystem crossing (photodynamic effect) and internal thermal conversion (photothermal effect). Thus, a heptamethine cyanine photosensitizer containing a binitro-substituted benzenesulfonamide (ER-Cy-poNO2 ) is identified that preferentially accumulates in the ER of tumor cells. It significantly enhances the phototherapeutic effect by inducing excessive ER stress and robust ICD. Consequently, this small molecular photosensitizer triggers a sufficient antitumor immune response and effectively suppresses the growth of both primary and distant metastatic tumors, whereas no apparent toxicity is observed. This heptamethine cyanine photosensitizer has the potential to enhance cancer-targeted immunotherapy.

Cerium oxide nanoparticles protect red blood cells from hyperthermia-induced damages.

Heat stroke and severe fever cause anemia, although the underlying mechanism remains unclear. Here, we report the use of Cerium oxide nanoparticles in protection of red blood cells against damage caused by exposure to short-term hyperthermia (42°C, 10 min). Red blood cells exposed to hyperthermia exhibited extradition senescence with higher density, smaller size and lower zeta potential relative to those under normal physiological environment (37°C, 10 min). Furthermore, hyperthermia-exposed cells exhibited significantly higher reactive oxygen species (ROS) production compared to the normal conditions. Importantly, the preconditional treatment, using Ceria nanoparticles (CNPs), ameliorated senescence and apoptosis in red blood cells damaged by hyperthermia by reducing ROS levels. Summarily, short-term hyperthermia caused a significant increase in ROS in red blood cells, and resulted in senescence and apoptosis. These may be possible mechanisms of pathological changes in red blood cells exposed to heat stroke or severe fever. Overall, these findings indicate that CNPs strongly inhibit ROS production, and effectively ameliorates hyperthermia-induced damages in red blood cells.